CGAS_NEMVE
ID CGAS_NEMVE Reviewed; 422 AA.
AC A7SFB5;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Cyclic GMP-AMP synthase {ECO:0000303|PubMed:26300263};
DE Short=NvcGAS {ECO:0000303|PubMed:30842662};
DE Short=cGAMP synthase {ECO:0000303|PubMed:26300263};
DE Short=cGAS {ECO:0000303|PubMed:26300263};
DE Short=nv-cGAS {ECO:0000303|PubMed:26300263};
DE EC=2.7.7.86 {ECO:0000269|PubMed:26300263};
DE AltName: Full=3'3'-cGAMP synthase {ECO:0000303|PubMed:26300263};
GN ORFNames=v1g211400;
OS Nematostella vectensis (Starlet sea anemone).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Edwardsiidae; Nematostella.
OX NCBI_TaxID=45351;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CH2 X CH6;
RX PubMed=17615350; DOI=10.1126/science.1139158;
RA Putnam N.H., Srivastava M., Hellsten U., Dirks B., Chapman J., Salamov A.,
RA Terry A., Shapiro H., Lindquist E., Kapitonov V.V., Jurka J.,
RA Genikhovich G., Grigoriev I.V., Lucas S.M., Steele R.E., Finnerty J.R.,
RA Technau U., Martindale M.Q., Rokhsar D.S.;
RT "Sea anemone genome reveals ancestral eumetazoan gene repertoire and
RT genomic organization.";
RL Science 317:86-94(2007).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF GLU-131 AND ASP-133.
RX PubMed=26300263; DOI=10.1016/j.molcel.2015.07.022;
RA Kranzusch P.J., Wilson S.C., Lee A.S., Berger J.M., Doudna J.A.,
RA Vance R.E.;
RT "Ancient origin of cGAS-STING reveals mechanism of universal 2',3' cGAMP
RT signaling.";
RL Mol. Cell 59:891-903(2015).
RN [3]
RP FUNCTION.
RX PubMed=30842662; DOI=10.1038/s41586-019-1006-9;
RA Gui X., Yang H., Li T., Tan X., Shi P., Li M., Du F., Chen Z.J.;
RT "Autophagy induction via STING trafficking is a primordial function of the
RT cGAS pathway.";
RL Nature 567:262-266(2019).
CC -!- FUNCTION: Nucleotidyltransferase that catalyzes the formation of cyclic
CC GMP-AMP (cGAMP) from ATP and GTP (PubMed:26300263, PubMed:30842662).
CC Catalysis involves both the formation of a 2',5' phosphodiester linkage
CC at the GpA step and the formation of a 3',5' phosphodiester linkage at
CC the ApG step, producing c[G(2',5')pA(3',5')p] (PubMed:26300263). Acts
CC as a key cytosolic DNA sensor, the presence of double-stranded DNA
CC (dsDNA) in the cytoplasm being a danger signal that triggers the immune
CC responses (By similarity). Binds cytosolic DNA directly, leading to
CC activation and synthesis of cGAMP, a second messenger that binds to and
CC activates v1g246111/STING (By similarity).
CC {ECO:0000250|UniProtKB:Q8C6L5, ECO:0000269|PubMed:26300263,
CC ECO:0000269|PubMed:30842662}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + GTP = 2',3'-cGAMP + 2 diphosphate; Xref=Rhea:RHEA:42064,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:143093; EC=2.7.7.86;
CC Evidence={ECO:0000269|PubMed:26300263};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8C6L5};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250|UniProtKB:Q8C6L5};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8C6L5}.
CC -!- SIMILARITY: Belongs to the mab-21 family. {ECO:0000305}.
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DR EMBL; DS469643; EDO37594.1; -; Genomic_DNA.
DR RefSeq; XP_001629657.1; XM_001629607.1.
DR AlphaFoldDB; A7SFB5; -.
DR SMR; A7SFB5; -.
DR EnsemblMetazoa; EDO37594; EDO37594; NEMVEDRAFT_v1g211400.
DR GeneID; 5509120; -.
DR KEGG; nve:5509120; -.
DR eggNOG; KOG3963; Eukaryota.
DR HOGENOM; CLU_651006_0_0_1; -.
DR InParanoid; A7SFB5; -.
DR OMA; KANRCRI; -.
DR OrthoDB; 759341at2759; -.
DR PhylomeDB; A7SFB5; -.
DR Proteomes; UP000001593; Unassembled WGS sequence.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0061501; F:2',3'-cyclic GMP-AMP synthase activity; IMP:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR InterPro; IPR024810; Mab-21_dom.
DR Pfam; PF03281; Mab-21; 1.
DR SMART; SM01265; Mab-21; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; GTP-binding; Magnesium; Metal-binding;
KW Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW Transferase.
FT CHAIN 1..422
FT /note="Cyclic GMP-AMP synthase"
FT /id="PRO_0000434974"
FT REGION 29..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 35..52
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 117
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 119
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 131
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 133
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 242
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 242
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 289..296
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 296
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 319
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 333..337
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT MUTAGEN 131
FT /note="E->A: Loss of activity; when associated with A-133."
FT /evidence="ECO:0000269|PubMed:26300263"
FT MUTAGEN 133
FT /note="D->A: Loss of activity; when associated with A-131."
FT /evidence="ECO:0000269|PubMed:26300263"
SQ SEQUENCE 422 AA; 49638 MW; 1736AF70D63F41EF CRC64;
MATLERLLDL LREYHLDDVL FHNSTPELGI QHRSRPKQKR IIRGKKQQKS KKLKRNEQQQ
PFPKGDLETL RRFSVTDVKI SKQSTKWAKK MADKHLEIIR KHCKTNSIKL FNHFEYTGSF
YEHLKTIDAD ELDIMVALSI KMDELEVEQV TPGYAGLKLR DTPSNRNKYN DLTIADNYGR
YLSPEKVSRW FFSLVQKAVN TYKDEIPQTE VKLTDNGPAT TLVITYREGD KPQEKNRRLS
IDLVPALLFK DKTKPAGDDL RAWHYVAKTI PKGARLKEPL PFRSELLWRQ SFSLKEKHLM
DKLDKDDNGC RREMVRIVKT IVKKDPTLAQ LSSYHIKTAF LQYNFSDVKL DWEGKKLAER
FLHFLEFLRD RVKDKTLNNY FITDLNLLDD LNDSNIDNIA NRLDKIIQNE TERAKIFTTQ
RQ
